FDA Guidelines for Demonstrating Biosimilarity

Well, the four steps that follow along with this chart are the analytical studies, analytical categories, the functional assays, the animal data, and the clinical studies. And, of course, if you are the biosimilar, you’re working with the right-side pyramid. And the clinical studies are very small. That’s what you want to avoid is the biosimilar because they’re the ones that are most expensive. Extremely long, most expensive. It takes ten to twelve years for an originator to get a product approved and on the market because of those clinical studies. The analytical information and growing the biological for the original developer, that’s very simple, very easy. It’s the clinical studies that are hard, could take eight years out of the twelve years.

Analytical studies, on the other hand, and functional studies on the other hand, for the biosimilar are what is the big deal. Now, remember that I said that the biological is not only the polypeptide, but it’s all the other stuff that comes along from the living cells. Just like wine, it’s got all this other stuff in it. So here you are as the biosimilar company and you have to demonstrate not only that you have the same primary product, the same polypeptide, but you’ve got the same other stuff as the originator. This is the analytical part. And so you’ve got to take a look at what the original product has in it, and you’ve got to show one-to-one correspondence almost that your product has the same side products in it, the same stuff, in addition to the polypeptide. Well, wait a minute. The originator is also making a biological. The originator has this same problem like wine from batch to batch, year to year, his product is gonna be different. All the stuff in his product varies all over the place.

So here you are, the biosimilar company, you’re the biosimilar producer and you want to produce something that is exactly the same as the originator, but the originator’s target is going all over the place. It’s varying. It’s here, it’s there, it’s everywhere. So you’re trying to shoot at this target and it’s moving. You can’t hit it. It’s extremely difficult. So that is the problem both with the analytical and the functional assay categories for the FDA Guidelines. Once you get past those and you do your animal data, toxicity and all that sort of thing, you’re pretty much home free. It’s those first two, analytical categories and functional assays, that provide these difficulties. And from the FDA’s point of view, if there’s a problem with your analytical and functional work, you can’t just go back and do a couple more studies and change things, fix the problem. The FDA says you have to go all the way back to the beginning and start over again. It makes it very difficult.